Down on his luck after a bitter divorce, Planetary Union officer Ed Mercer finally gets his chance to command his own ship, the Orville, a not-so-top-of-the-line exploratory ship in Earth's interstellar Fleet.

Determined to prove his worth and start a new chapter, Ed discovers the first wrinkle in his plan when the First Officer assigned to his ship is his ex-wife, Kelly Grayson. As the new commander, Ed assembles a qualified - but eccentric - crew, including his best friend, Gordon, who has problems with authority but is the best helmsman in the fleet; Dr. Claire Finn; Bortus, an alien from a single-sex species; Isaac, an artificial life-form from a machine society; navigator John Lamarr; Alara Kitan, a young, inexperienced security officer; and Yaphit, a gelatinous creature.

Facing cosmic challenges from without and within, this motley crew of space explorers will boldly go where no comedic drama has gone before.